Many nutritional supplements are available at various retail outlets, in many forms, including tablets, pills, powders, and liquids intended for human consumption.
One nutritional supplement that has become popular is creatine, whose IUPAC name is 2-(carbamimidoyl-methyl-amino) acetic acid (CAS No. 57-00-1). Creatine occurs naturally in muscle and is believed to be an essential component in energy-producing metabolism and normal muscle function and growth. It is also believed by many to be useful to bodybuilders for increasing muscle mass, i.e., muscle-building.
Creatine supplementation offers a variety of health benefits. Studies have shown that creatine enhances athletic performance in the strength-power sports, promotes gains in lean body mass and muscle fiber hypertrophy (growth), improves neuromuscular function, especially in patients with metabolic diseases and decreased muscular fitness, and improves neural function and cognitive abilities. In addition, no adverse health effect has been observed in both short- or long-term creatine supplementations. In a thorough scientific review published in the Journal of Strength and Conditioning, scientists summarized 22 published studies, and concluded that the average increase in muscle strength following creatine supplementation during resistance training was 8% greater than the average increase in muscle strength following placebo ingestion during resistance training (20% vs. 12%). Also, the average increase in weightlifting performance (maximal repetitions at a given percent of maximal strength) following creatine supplementation during resistance training was 14% greater than the average increase in weightlifting performance following placebo ingestion during resistance training (26% vs. 12%). In addition, creatine supplementation improves the bench press 1-Rep Max (RM) performance of 3% to 45%, and the weightlifting performance in the bench press of 16% to 43%.(1)
In addition, scientists tested the hypothesis whether oral creatine supplementation 5 grams daily for six weeks would enhance intelligence test scores and working memory performance in 45 young adult, vegetarian subjects in a double-blind, placebo-controlled, cross-over design. The results showed that creatine supplementation significantly improves both working memory (backward digit span) and intelligence (Raven's Advanced Progressive Matrices).(2)
Furthermore, creatine supplementation has neuroprotective effects, useful for preventing and treating neurological diseases such as Huntington's disease, Parkinson's disease, or amyotrophic lateral sclerosis.(3) One investigation found that 5 grams of creatine supplementation daily, coupled with resistance training (3× per week for 15 weeks), improved physical function in a 26-year-old man with myasthenia gravis. This individual had a 7% increase in body weight, 4% increase in fat free mass, and improved peak strength up to 37%. (4) Another investigation found that creatine supplementation improves skeletal muscle function in patients with McArdle disease.(5)
In addition, creatine supplementation significantly enhances muscular fitness of patients with Parkinson disease (PD), who exhibit decreased muscular fitness, including decreased muscle mass, muscle strength, and increased fatigability. Twenty patients with idiopathic PD were randomized to receive creatine monohydrate supplementation during resistance training (CRE) or placebo (lactose monohydrate) during resistance training (PLA), using a double-blind procedure. Both the creatine and placebo supplementation consisted of 20 g/d for the first 5 days and 5 g/d thereafter. Both groups participated in progressive resistance training (24 sessions, 2 times per week, 1 set of 8-12 repetitions, 9 exercises). Creatine supplementation significantly improved chest press strength and biceps curl strength.(7)
There are also data concerning the short and long-term therapeutic benefits of creatine supplementation in children and adults with gyrate atrophy (a result of the inborn error of metabolism with ornithine delta-aminotransferase activity), muscular dystrophy (facioscapulohumeral dystrophy, Becker dystrophy, Duchenne dystrophy and sarcoglycan deficient limb girdle muscular dystrophy), McArdle's disease, Huntington's disease and mitochondria-related diseases. Hypoxia and energy related brain pathologies (brain trauma, cerebral ischemia, prematurity) could benefit from Cr supplementation.(12) Creatine supplementation has also been shown to lead to an improvement in various cognitive tasks.(13)
More beneficially, there is no scientific evidence that the short- or long-term use of creatine monohydrate has any detrimental effects on otherwise healthy individuals. In fact, five days of creatine supplementation enhances the dynamic strength and may increase anaerobic metabolism in the lower extremity muscles, and improves performance in consecutive maximal swims in highly trained adolescent (mean age 16) fin swimmers.(11)
No adverse effects on renal function has been observed in short term (5 days), medium term (9 weeks) and long term (up to 5 years) oral creatine supplementation in small cohorts of athletes.(8) Another investigation examined over a 21-month period, 98 Division IA college football players who consumed in an open label manner creatine or non-creatine containing supplements following training sessions. Subjects who ingested creatine were administered 15.75 g/day of creatine monohydrate for five days and an average of 5 g/day thereafter in 5-10 g/day doses. No adverse effect has been observed in long-term creatine supplementation (up to 21-months).(9)
According to the position stand published by the International Society of Sports Nutrition(10), creatine is the most effective ergogenic nutritional supplement currently available to athletes in terms of increasing high-intensity exercise capacity and lean body mass during training. Also, supplementation is not only safe, but possibly beneficial in regard to preventing injury and/or management of select medical conditions when taken within recommended guidelines.
Despite its significant health benefits, creatine supplementation can only be offered in powder, pill or capsule form. Currently, no aqueous-based formulation containing appreciable amounts of creatine, intended for oral human consumption, is available in the marketplace. This is because creatine is unstable in aqueous systems, in which it rearranges to creatinine.
The rate of creatine degradation in aqueous systems can be determined based on serum creatinine concentration. Creatine is non-enzymatically converted into creatinine at approximately 1.7% daily in a typical 70 kg individual. The skeletal muscle represents the primary site of creatinine production. Creatine is also degraded in the GI tract into creatinine at an estimated rate of 0.1 g of a 5 g dose per hour.
Creatinine has no nutritional benefits and does not enhance muscle fitness. Moreover, abnormal serum creatinine levels may be correlated with serious disease or renal dysfunction. For example, blood creatinine levels are used as a measure of renal function, and abnormally high levels indicate possible renal dysfunction.
Conditions leading to high blood creatinine levels further include blockage of the urinary tract (such as by a kidney stone), heart failure, dehydration, excessive blood loss that causes shock, gout, or muscle conditions (such as rhabdomyolysis, gigantism, acromegaly, myasthenia gravis, muscular dystrophy, and polymyositis). Usually a high blood creatinine level means that the creatinine clearance value is lower than normal.
There is a critical need in the art for a creatine composition that is stable in aqueous systems.